Evolutionarily stable learning schedules and cumulative culture in discrete generation models.

Individual learning (e.g., trial-and-error) and social learning (e.g., imitation) are alternative ways of acquiring and expressing the appropriate phenotype in an environment. The optimal choice between using individual learning and/or social learning may be dictated by the life-stage or age of an organism. Of special interest is a learning schedule in which social learning precedes individual learning, because such a schedule is apparently a necessary condition for cumulative culture. Assuming two obligatory learning stages per discrete generation, we obtain the evolutionarily stable learning schedules for the three situations where the environment is constant, fluctuates between generations, or fluctuates within generations. During each learning stage, we assume that an organism may target the optimal phenotype in the current environment by individual learning, and/or the mature phenotype of the previous generation by oblique social learning. In the absence of exogenous costs to learning, the evolutionarily stable learning schedules are predicted to be either pure social learning followed by pure individual learning ("bang-bang" control) or pure individual learning at both stages ("flat" control). Moreover, we find for each situation that the evolutionarily stable learning schedule is also the one that optimizes the learned phenotype at equilibrium.

Mixing of Rhône River water in Lake Geneva (Switzerland-France) inferred from stable hydrogen and oxygen isotope profiles

Depth profiles were sampled at different locations throughout Lake Geneva on a monthly and seasonal basis over the course of 2 years and analysed for their stable hydrogen and oxygen isotope compositions. The isotopic compositions indicate an isotopic stratification in the metalimnion during summer and fall. This is related to mixing of Rhône River water, which in summer is dominated by snow and glacier melt waters, and lake water, with the latter having a homogenous isotopic composition. The observed interflow layer is 7-15 m thick and can be traced by the distinct stable isotope composition of the water for about 55 km throughout the lake as well as into shallow bay regions. Depth of the interflow layer close to the Rhône River mouth is similar to those previously described based on echo-soundings and turbidity profiles of sediment dispersion. In contrast to previous descriptions of the interflow within Lake Geneva, the stable isotope compositions allow for direct, natural tracing of the Rhône River water even in cases where the turbidity and conductivity measurements do not indicate such an interflow. In addition, the method allows for a quantification of the Rhône River and lake water in the interflow with the fraction of Rhône River water within the interflow estimated to be up to 37% in summer. The isotopic composition further indicates different vertical mixing processes within the two lake basins of Lake Geneva, related to the density gradients and local stability within the water column. The method may be applicable to other lakes in catchments with large differences in the topography as water that originates from high altitudes or glaciers has a distinct oxygen and hydrogen isotope composition compared to other sources of water originating at lower altitudes and/or from direct precipitation over the lake. Stable isotope measurements thus improve the understanding of the circulation of water within the lake, which is fundamental for an evaluation of the water residence times, dissolved pollutant and nutrient transport as well as oxygenation.

Development of stable cell lines for production or regulated expression using matrix attachment regions.

One of the major hurdles of isolating stable, inducible or constitutive high-level producer cell lines is the time-consuming selection procedure. Given the variation in the expression levels of the same construct in individual clones, hundreds of clones must be isolated and tested to identify one or more with the desired characteristics. Various boundary elements (BEs), matrix attachment regions, and locus control regions (LCRs) were screened for their ability to augment the expression of heterologous genes in Chinese hamster ovary (CHO) cells. Of the chromatin elements assayed, the chicken lysozyme matrix-attachment region (MAR) was the only element to significantly increase stable reporter expression. We found that the use of the MAR increases the proportion of high-producing clones, thus reducing the number of clones that need to be screened. These benefits are observed both for constructs with MARs flanking the transgene expression cassette, as well as when constructs are co-transfected with the MAR on a separate plasmid. Moreover, the MAR was co-transfected with a multicomponent regulatable beta-galactosidase expression system in C2C12 cells and several clones exhibiting regulated expression were identified. Hence, MARs are useful in the development of stable cell lines for production or regulated expression.

Quantification of magmatic and hydrothermal processes in a peralkaline syenite-alkali granite complex based on textures, phase equilibria, and stable and radiogenic isotopes

The Puklen complex of the Mid-Proterozoic Gardar Province, South Greenland, consists of various silica-saturated to quartz-bearing syenites, which are intruded by a peralkaline granite. The primary mafic minerals in the syenites are augite +/- olivine + Fe-Ti oxide + amphibole. Ternary feldspar thermometry and phase equilibria among mafic silicates yield T = 950-750degreesC, a(SiO2) = 0.7-1 and an f(O2) of 1-3 log units below the fayalite-magnetite-quartz (FMQ) buffer at 1 kbar. In the granites, the primary mafic minerals are ilmenite and Li-bearing arfvedsonite, which crystallized at temperatures below 750degreesC and at f(O2) values around the FMQ buffer. In both rock types, a secondary post-magmatic assemblage overprints the primary magmatic phases. In syenites, primary Ca-bearing minerals are replaced by Na-rich minerals such as aegirine-augite and albite, resulting in the release of Ca. Accordingly, secondary minerals include ferro-actinolite, (calcite-siderite)(ss), titanite and andradite in equilibrium with the Na-rich minerals. Phase equilibria indicate that formation of these minerals took place over a long temperature interval from near-magmatic temperatures down to similar to300degreesC. In the course of this cooling, oxygen fugacity rose in most samples. For example, late-stage aegirine in granites formed at the expense of arfvedsonite at temperatures below 300degreesC and at an oxygen fugacity above the haematite-magnetite (HM) buffer. The calculated delta(18)O(melt) value for the syenites (+5.9 to +6.3parts per thousand) implies a mantle origin, whereas the inferred delta(18)O(melt) value of <+5.1parts per thousand for the granitic melts is significantly lower. Thus, the granites require an additional low-delta(18)O contaminant, which was not involved in the genesis of the syenites. Rb/Sr data for minerals of both rock types indicate open-system behaviour for Rb and Sr during post-magmatic metasomatism. Neodymium isotope compositions (epsilonNd(1170 Ma) = -3.8 to -6.4) of primary minerals in syenites are highly variable, and suggest that assimilation of crustal rocks occurred to variable extents. Homogeneous epsilon(Nd) values of -5.9 and -6.0 for magmatic amphibole in the granites lie within the range of the syenites. Because of the very similar neodymium isotopic compositions of magmatic and late- to post-magmatic minerals from the same syenite samples a principally closed-system behaviour during cooling is implied. In contrast, for the granites an externally derived fluid phase is required to explain the extremely low epsilon(Nd) values of about -10 and low delta(18)O between +2.0 and +0.5parts per thousand for late-stage aegirine, indicating an open system in the late-stage history. In this study we show that the combination of phase equilibria constraints with stable and radiogenic isotope data on mineral separates can provide much better constraints on magma evolution during emplacement and crystallization than conventional whole-rock studies.

Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure?

OBJECTIVE: To investigate whether HIV-infected patients on a stable and fully suppressive combination antiretroviral therapy (cART) regimen could safely be monitored less often than the current recommendations of every 3 months. DESIGN: Two thousand two hundred and forty patients from the EuroSIDA study who maintained a stable and fully suppressed cART regimen for 1 year were included in the analysis. METHODS: Risk of treatment failure, defined by viral rebound, fall in CD4 cell count, development of new AIDS-defining illness, serious opportunistic infection or death, in the 12 months following a year of a stable and fully suppressed regimen was assessed. RESULTS: One hundred thirty-one (6%) patients experienced treatment failure in the 12 months following a year of stable therapy, viral rebound occurred in 99 (4.6%) patients. After 3, 6 and 12 months, patients had a 0.3% [95% confidence interval (CI) 0.1-0.5], 2.2% (95% CI 1.6-2.8) and 6.0% (95% CI 5.0-7.0) risk of treatment failure, respectively. Patients who spent more than 80% of their time on cART with fully suppressed viraemia prior to baseline had a 38% reduced risk of treatment failure, hazard ratio 0.62 (95% CI 0.42-0.90, P = 0.01). CONCLUSION: Patients who have responded well to cART and are on a well tolerated and durably fully suppressive cART regimen have a low chance of experiencing treatment failure in the next 3-6 months. Therefore, in this subgroup of otherwise healthy patients, it maybe reasonable to extend visit intervals to 6 months, with cost and time savings to both the treating clinics and the patients.

Climatic and anthropogenic influence on the stable isotope record from bulk carbonates and ostracodes in Lake Neuchatel, Switzerland, during the last two millennia

Lake Neuchatel is a medium sized, hard-water lake, lacking varved sediments, situated in the western Swiss Lowlands at the foot of the Jura Mountains. Stable isotope data (delta(18)O and delta(13)C) from both bulk carbonate and ostracode calcite in an 81 cm long, radiocarbon-dated sediment core represent the last 1500 years of Lake Neuchatel's environmental history. Comparison between this isotopic and other palaeolimnologic data (mineralogical, geochemical, palynological, etc.) helps to differentiate between anthropogenic and natural factors most recently affecting the lake. An increase in lacustrine productivity (450-650AD ca), inferred from the positive trend in delta(13)C values of bulk carbonate, is related to medieval forest clearances and the associated nutrient budget changes. A negative trend in both the bulk carbonate and ostracode calcite delta(18)O values between approximately 1300 and 1500AD, is tentatively interpreted as due to a cooling in mean air temperature at the transition from the Medieval Warm Period to the Little Ice Age. Negative trends in bulk carbonate delta(18)O and delta(13)C values through the uppermost sediments, which have no equivalent in ostracode calcite isotopic values, are concomitant with the recent onset of eutrophication in the lake. Isotopic disequilibrium during calcite precipitation, probably due to kinetic factors in periods of high productivity is postulated as the mechanism to explain the associated negative isotopic trends, although the effect of a shift of the calcite precipitation towards the warmer months cannot be excluded.

Association of biomarkers of lipid modification with functional and morphological indices of coronary stenosis severity in stable coronary artery disease.

Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.

Stable masking by H-2Dd cis ligand limits Ly49A relocalization to the site of NK cell/target cell contact.

Ly49A is an inhibitory receptor, which counteracts natural killer (NK) cell activation on the engagement with H-2D(d) (D(d)) MHC class I molecules (MHC-I) on target cells. In addition to binding D(d) on apposed membranes, Ly49A interacts with D(d) ligand expressed in the plane of the NK cells' membrane. Indeed, multivalent, soluble MHC-I ligand binds inefficiently to Ly49A unless the NK cells' D(d) complexes are destroyed. However, it is not known whether masked Ly49A remains constitutively associated with cis D(d) also during target cell interaction. Alternatively, it is possible that Ly49A has to be unmasked to significantly interact with its ligand on target cells. These two scenarios suggest distinct roles of Ly49A/D(d) cis interaction for NK cell function. Here, we show that Ly49A contributes to target cell adhesion and efficiently accumulates at synapses with D(d)-expressing target cells when NK cells themselves lack D(d). When NK cells express D(d), Ly49A no longer contributes to adhesion, and ligand-driven recruitment to the cellular contact site is strongly reduced. The destruction of D(d) complexes on NK cells, which unmasks Ly49A, is necessary and sufficient to restore Ly49A adhesive function and recruitment to the synapse. Thus, cis D(d) continuously sequesters a considerable fraction of Ly49A receptors, preventing efficient Ly49A recruitment to the synapse with D(d)+ target cells. The reduced number of Ly49A receptors that can functionally interact with D(d) on target cells explains the modest inhibitory capacity of Ly49A in D(d) NK cells. This property renders Ly49A NK cells more sensitive to react to diseased host cells.

Oxidation of methane at the CH4/H2O-(CO2) transition zone in the external part of the Central Alps, Switzerland: Evidence from stable isotope investigations

With the aim of understanding the mechanisms that control the metamorphic transition from the CH4- to the H2O-(CO2)-dominated fluid zone in the Helvetic domain of the Central Alps of Switzerland, fluid inclusions in quartz, illite ``crystallinity'' index, vitrinite reflectance, and the stable isotope compositions of vein and whole rock minerals and fluids trapped in quartz were investigated along four cross-sections. Increasing temperature during prograde metamorphism led to the formation of dry gas by hydrocarbon cracking in the CH4-zone. Fluid immiscibility in the H2O-CH4-(CO2)-NaCl system resulted in cogenetic, CH4- and H2O-dominated fluid inclusions. In the CH4-zone, fluids were trapped at temperatures <= 270 +/- 5 degrees C. The end of the CH4-zone is markedby a sudden increase of CO2 content in the gas phase of fluid inclusions. At temperatures > 270 +/- 5 degrees C, in the H2O-zone, the total amount of volatiles within the fluid decreased below 1 mol% with no immiscibility. This resulted m total homogenization temperatures of H2O-(CO2-CH4)-NaCl inclusions below 180 degrees C. Hydrogen isotope compositions of methane in fluid inclusion have delta D values of less than -100 parts per thousand in the CH4-zone, typical for an origin through cracking of higher hydrocarbons, but where the methane has not equilibrated with the pore water. delta D values of fluid inclusion water are around -40 parts per thousand., in isotopic equilibrium with phyllosilicates of the whole rocks. Within the CH4 to H2O(CO2) transition zone, delta D(H2O) values in fluid inclusions decrease to -130 parts per thousand interpreted to reflect the contribution of deuterium depleted water from methane oxidation. In the H2O-zone, delta D(H2O) values increase again towards an average of -30 parts per thousand which is again consistent with isotopic equilibrium with host-rock phyllosilicates. delta C-13 values of methane in fluid inclusions from the CH4-zone are around -27 parts per thousand in isotopic equilibrium with calcite in veins and whole rocks. The delta C-13(CH4) values decrease to less than -35 parts per thousand at the transition to the H2O-zone and are no longer in equilibrium with the carbonates in the whole rocks. delta C-13 values of CO, are variable but too low to be in equilibrium with the wall rock fluids, compatible with a contribution of CO2 from closed system oxidation of methane. Differences in isotopic composition between host-rock and Alpine fissure carbonate are generally small, suggesting that the amount of CO2 produced by oxidation of methane was small compared to the C-budget in the rocks and local pore fluids were buffered by the wall rocks during precipitation of calcite within the fissures. (c) 2006 Elsevier B.V. All rights reserved.

Stable isotope (C, O, S) systematics of the mercury mineralization at Idrija, Slovenia: constraints on fluid source and alteration processes

The world-class Idrija mercury deposit (western Slovenia) is hosted by highly deformed Permocarboniferous to Middle Triassic sedimentary rocks within a complex tectonic structure at the transition between the External Dinarides and the Southern Alps. Concordant and discordant mineralization formed concomitant with Middle Triassic bimodal volcanism in an aborted rift. A multiple isotopic (C, O, S) investigation of host rocks and ore minerals was performed to put constraints on the source and composition of the fluid, and the hydrothermal alteration. The distributions of the delta(13)C and delta(18)O values of host and gangue carbonates are indicative of a fracture-controlled hydrothermal system, with locally high fluid-rock ratios. Quantitative modeling of the delta(13)C and delta(18)O covariation for host carbonates during temperature dependent fluid-rock interaction, and concomitant precipitation of void-filling dolomites points to a slightly acidic hydrothermal fluid (delta(13)Capproximate to-4parts per thousand and delta(18)Oapproximate to+10parts per thousand), which most likely evolved during isotopic exchange with carbonates under low fluid/rock ratios. The delta(34)S values of hydrothermal and sedimentary sulfur minerals were used to re-evaluate the previously proposed magmatic and evaporitic sulfur sources for the mineralization, and to assess the importance of other possible sulfur sources such as the contemporaneous seawater sulfate, sedimentary pyrite, and organic sulfur compounds. The delta(34)S values of the sulfides show a large variation at deposit down to hand-specimen scale. They range for cinnabar and pyrite from -19.1 to +22.8parts per thousand, and from -22.4 to +59.6parts per thousand, respectively, suggesting mixing of sulfur from different sources. The peak of delta(34)S values of cinnabar and pyrite close to 0parts per thousand is compatible with ore sulfur derived dominantly from a magmatic fluid and/or from hydrothermal leaching of basement rocks. The similar stratigraphic trends of the delta(34)S values of both cinnabar and pyrite suggest a minor contribution of sedimentary sulfur (pyrite and organic sulfur) to the ore formation. Some of the positive delta(34)S values are probably derived from thermochemical reduction of evaporitic and contemporaneous seawater sulfates.

Apparent stable-isotope heterogeneities in gangue carbonates of the Mississippi Valley-type Zn-Pb deposits of San-Vicente, Central Peru

The aim of the present communication is to emphasize that some variations of the measured delta(13)C and delta(18)O values are apparent, and due to analytical interferences caused by the presence of sulfur and organosulfur compounds in the analyzed carbonates. This is particularly relevant for isotopic studies on carbonate-hosted mineral deposits, where the nearly ubiquitous association of the host carbonates with organic matter and sulfides can certainly affect the metallogenetic interpretations. In this work two methods were used to overcome the disturbing effects of sulfides and organic matter: (1) sample pretreatment following the method proposed by Charef and Sheppard (1984), combining the oxidation of organic matter with sodium hypochlorite and trapping of the sulfur species with silver phosphate; and (2) laser-based microprobe extraction. Apparent isotopic variations in sparry dolomite from a single hand sample of zebra ore from the MVT Zn-Pb deposit, San Vicente, central Peru, are as large as 6 parts per thousand delta(13)C and 4 parts per thousand delta(18)O. These variations are reduced to several tenths of a per mil when the samples are pretreated. A careful examination of the effects of treatment with NaOCl and/or Ag3PO4 in relation to the concentration of sulfide inclusions indicates that the main disturbing effects for delta(13)C values are the presence of sulfur species and organic matter, whereas the delta(18)O values are mainly affected by the presence of sulfides. Fine- and medium-grained replacement carbonates from MVT and other sediment-hosted base metal deposits are potentially the most affected during isotope analysis, due to the common presence of organic matter and sulfides. Using in situ laser microprobe techniques, it is possible to determine isotopic variations at a sub-millimeter scale. Our results show that laser extraction analysis allows a more precise sampling of the carbonate minerals, and minimizes contamination of the sample with sulfides and to some extent with intergrown organic matter. However, there is an isotopic shift associated with the laser extraction technique, of the order of 0.5-1 parts per thousand for delta(13)C and delta(18)O values.

Tracing of the Rhône River, wastewater, and mixing within Lake Geneva : stable isotope compositions of water and dissolved inorganic carbon

This study presents an evaluation of the stable isotopic composition of water (hydrogen and oxygen) and dissolved inorganic carbon (DIC) of Lake Geneva, a deep, peri-alpine lake situated at the border between Switzerland and France. The research goal is to apply vertical and seasonal variations of the isotope compositions to evaluate mixing processes of pollutants, nutrients and oxygen. Depth profiles were sampled at different locations throughout Lake Geneva on a monthly and seasonal basis over the course of three years (2009-2011). The results of the oxygen isotopic composition indicate a Rhône River interflow, which can be traced for about 55 km throughout the lake during summer. The Rhône River interflow is 7 to 15 m thick and the molar fraction of Rhône water is estimated to amount up to 37 %. Calculated density of the water and measured isotopic compositions demonstrate that the interflow depth changes in conjunction with the density gradient in the water column during fall. Partial pressure of CO2 indicates that the epilimnion is taking up CO2 from the atmosphere between spring and fall. The epilimnion is most enriched in 13CDIC in September and a progressive depletion of 13CDIC can be observed in the metalimnion from spring to late fall. This stratification is dependent on the local density stratification and the results demonstrate that parameters, which are indicating photosynthesis, are not necessarily linked to δ13CDIC values. In addition, the amount of primary production shows a strong discrepancy between summer 2009 and 2010, but δ13CDIC values of the epilimnion and metalimnion do not indicate variations. In the hypolimnion of the deep lake δ13CDIC values are constant and the progressive depletion allows tracing remineralization processes. The combination of stable carbon and oxygen isotopic compositions allows furthermore tracing Rhône River water fractions, as well as wastewater, stormwater and anthropogenic induced carbon in the water column of the shallow Bay of Vidy. In combination with the results of measured micropollutants, the study underlines that concentrations of certain substances may be related to the Rhône River interflow and/or remineralization of particulate organic carbon. Water quality monitoring and research should therefore be extended to the metalimnion as well as sediment water interface.

Study of isotopic variations in black powder: reflections on the use of stable isotopes in forensic science for source inference.

Isotope ratio mass spectrometry (IRMS) has recently made its appearance in the forensic community. This high-precision technology has already been applied to a broad range of forensic fields such as illicit drugs, explosives and flammable liquids, where current, routinely used techniques have limited powers of discrimination. The conclusions drawn from the majority of these IRMS studies appear to be very promising. Used in a comparative process, as in food or drug authentication, the measurement of stable isotope ratios is a new and remarkable analytical tool for the discrimination or the identification of a substance with a definite source or origin. However, the research consists mostly of preliminary studies. The significance of this 'new' piece of information needs to be evaluated in light of a forensic framework to assess the actual potential and validity of IRMS, considering the characteristics of each field. Through the isotopic study of black powder, this paper aims at illustrating the potential of the method and the limitations of current knowledge in stable isotopes when facing forensic problems.